The molecular signature of AML mesenchymal stromal cells reveals candidate genes related to the leukemogenic process

Binato, Renata; Oliveira, Nathalia Correa de Almeida; Rocher, Bárbara Du; Abdelhay, Eliana

doi:10.1016/j.canlet.2015.08.006

Cited by 18 publications

(27 citation statements)

References 38 publications

(44 reference statements)

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“…Molecular signatures associated with distinct prognosis have been illustrated in many different cancers [24], [25], [26], [27], [28]. For breast cancer, a 21-gene signature has even been approved by the FDA for application in bedside decisions [24], [29].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

Min

Zhao

Zhu

et al. 2017

Translational Oncology

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BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters. RESULTS: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ2 = 30.71, P < .001) that exhibits better discrimination for prognosis than Lauren classification (χ2 = 12.11, P = .002). FRZB [RR (95% CI) = 1.824 (1.115-2.986), P = .017] and EFEMP1 [RR (95% CI) = 1.537 (0.969-2.437), P = .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI) = 1.616 (0.938-2.785), P = .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort. CONCLUSION: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

Min

Zhao

Zhu

et al. 2017

Translational Oncology

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“…Transcriptome abnormalities were also observed in human BM-MSCs of acute myeloid leukaemia (Huang, J.C. et al, 2015) and multiple sclerosis patients . A number of candidate genes relating to the leukemic transformation process were identified (Binato et al, 2015;Huang, J.C. et al, 2015). Analysis of the transcriptome and micro RNAs of breast resident AD-MSCs revealed that migrating cells displayed similar profiles to those of resident AD-MSCs in this condition, suggesting a role of resident AD-MSCs in breast cancer development (Senst et al, 2013).…”

Section: Exploring Disease Associationmentioning

confidence: 97%

“…Disease association is another application of comparative transcriptome analysis to MSC populations derived from control and pathological states (Benisch et al, 2012;Binato et al, 2015;de Oliveira et al, 2015;Huang, J.C. et al, 2015;Li et al, 2012). Remarkable abnormality in gene expression was observed in human BM-MSCs from aplastic anaemia patients when compared with those from healthy volunteers (Li et al, 2012).…”

Section: Exploring Disease Associationmentioning

confidence: 97%

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Kasoju

Wang

Zhang

et al. 2017

Biotechnology Advances

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The plastic-adherent, fibroblast-like, clonogenic cells found in the human body now defined as multipotent "Mesenchymal Stromal Cells" (MSCs) hold immense potential for cell-based therapies. Recently, research and basic knowledge of these cells has fast-tracked, both from fundamental and translational perspectives. There have been important discoveries with respect to the available variety of tissue sources, the development of protocols for their easy isolation and in vitro expansion and for directed differentiation into various cell types. In addition, there has been discovery of novel abilities such as immune-modulation and further development of the use of biomaterials to aid isolation, expansion and differentiation together with improved delivery to the selected optimal tissue site. However, the molecular fingerprint of MSCs in these contexts remains imprecise and inadequate. Consequently, without this crucial knowledge it is difficult to achieve progress to determine with precision their practical developmental potentials. Detailed investigations on the global gene expression, or transcriptome, of MSCs could offer essential clues in this regard. In this article, we address the challenges associated with MSC transcriptome studies, the paradoxes observed in published experimental results and the need for careful transcriptomic analysis. We describe the exemplary applications with various transcriptome platforms that are used to address the variation in biomarkers and the identification of differentiation processes. The evolution and the potentials for adapting next-generation sequencing (NGS) technology in transcriptome analysis are discussed. Lastly, based on review of the existing understanding and published studies, we propose how NGS may be applied to promote further understanding of the biology of MSCs and their use in allied fields such as regenerative medicine.

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“…Extrinsic factors including cytokine secretion controlled by proinflammatory and nuclear factor κB cell (NF‐κB) pathways within MSCs also contribute to abnormalities in patient‐derived samples. These include altered production of interleukin‐6 (IL‐6), VEGF, C‐C motif chemokine ligand 2 (CCL2), IL‐8, and interferon γ . The notion that this might provide a competitive advantage to leukemia cells is corroborated by a study wherein inhibition of the NF‐κB pathway in AML‐MSCs reduced extrinsic chemoprotection and enhanced therapy‐induced apoptosis in AML blasts .…”

Section: Functional and Molecular Changes In Patient‐derived Stromamentioning

confidence: 99%

Concise Review: Adaptation of the Bone Marrow Stroma in Hematopoietic Malignancies: Current Concepts and Models

2018

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The bone marrow stroma maintains hematopoiesis and coordinately regulates regenerative responses through dynamic interactions with hematopoietic stem and progenitor cells. Recent studies indicate that stromal components in the bone marrow of leukemia patients undergo a process of successive adaptation that in turn exerts dramatic effects on the hematopoietic stem cell compartment and promotes leukemic drug resistance. Therefore, functional changes in discrete marrow stromal populations can be considered an aspect of leukemia biogenesis in that they create an aberrant, self-reinforcing microenvironment. In this review, we will describe the current understanding of the remodeling of the hematopoietic stem cell niche following invasion by leukemia cells. We place emphasis on existing evidence of how mesenchymal stem cells and their progeny facilitate neoplastic growth and describe available models and analytical techniques to understand the conversion of the niche toward disease persistence. STEM CELLS 2018;36:304-312 SIGNIFICANCE STATEMENTThere is increasing awareness that the bone marrow microenvironment is a critical contributor to therapeutic resistance and relapse progression in hematological malignancies. Experimental evidence discussed herein highlights key aspects of the stromal conversion by leukemia and the resulting aberrant signaling within the niche. This article discusses the advantages and limitations of available experimental model system and emphasizes open scientific questions and opportunities.

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The molecular signature of AML mesenchymal stromal cells reveals candidate genes related to the leukemogenic process

Cited by 18 publications

References 38 publications

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Concise Review: Adaptation of the Bone Marrow Stroma in Hematopoietic Malignancies: Current Concepts and Models

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